The Role of FANCD2 in Determining Cellular Resistance to Ionizing Radiation

Kuhnert, V.M.; Kachnic, Lisa A.; Li, L.; Purschke, M. L.; Lee, R.; Dunst, Jürgen; Held, Kathryn D.; Willers, Henning

doi:10.1016/j.ijrobp.2007.07.1894

Cited by 1 publication

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using two different assays, we found that H 2 O 2 -treated PD20 cells exhibited elevated levels of apoptosis compared to the wild-type complemented cells ( Figure 4(d) ). In contrast, MMC treatment does not typically induce increased apoptosis in FANC-deficient cells [ 38 , 39 ]. Altogether, our data suggest that the mode of cell death following oxidative damage is not related to chromosomal aberrations that may arise due to failed repair of stalled replication forks.…”

Section: Resultsmentioning

confidence: 99%

“…Specifically, FANCA-mutant cells were not found to be sensitive to DNA damage caused by H 2 O 2 despite an inability to form FANCD2 foci ( Figure 2 ). In addition, we found that the MMC hypersensitivity, but not the H 2 O 2 hypersensitivity, of FANCD2-deficient fibroblasts was associated with an abrogation of RAD51 foci formation ( Figure 3 ) [ 38 ], suggesting different cellular responses to the two agents. Of note, previous data on the ability of FA cells to form damage-induced RAD51 foci have been somewhat inconsistent, possibly a reflection of the cell type under study and the particular assay conditions [ 9 – 13 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Biomarkers and Mechanisms of FANCD2 Function

Willers

Kachnic

Luo

et al. 2008

BioMed Research International

View full text Add to dashboard Cite

Genetic or epigenetic inactivation of the pathway formed by the Fanconi anemia (FA) and BRCA1 proteins occurs in several cancer types, making the affected tumors potentially hypersensitive to DNA cross-linkers and other chemotherapeutic agents. It has been proposed that the inability of FA/BRCA-defective cells to form subnuclear foci of effector proteins, such as FANCD2, can be used as a biomarker to aid individualization of chemotherapy. We show that FANCD2 inactivation not only renders cells sensitive to cross-links, but also oxidative stress, a common effect of cancer therapeutics. Oxidative stress sensitivity does not correlate with FANCD2 or RAD51 foci formation, but associates with increased γH2AX foci levels and apoptosis. Therefore, FANCD2 may protect cells against cross-links and oxidative stress through distinct mechanisms, consistent with the growing notion that the pathway is not linear. Our data emphasize the need for multiple biomarkers, such as γH2AX, FANCD2, and RAD51, to capture all pathway activities.

show abstract

Section: Resultsmentioning

confidence: 99%